1. Field of the Invention
The invention relates to a hydroxyalkyl alkyl cellulose, a method for producing the hydroxyalkyl alkyl cellulose, and a solid preparation comprising the hydroxyalkyl alkyl cellulose.
2. Related Art
A sustained-release preparation enables control of the concentration of an active ingredient dissolved in the blood at a certain level or less, or reduction of the number of administrations, so that it is useful. The sustained-release preparation is roughly classified into a single unit type and a multiple unit type. The single unit type preparation gradually releases an active ingredient to exhibit sustained-release characteristics, while maintaining the dosage form thereof in the gastrointestinal tract. Examples of the single unit type preparation include a matrix type preparation that is produced by tableting a mixture containing a water-soluble polymer or a wax. The multiple unit type preparation is a tablet or a capsule that is immediately disintegrated on administration to discharge granules, wherein the granules have been produced by coating a drug with a polymer film and exhibit sustained-release characteristics.
The matrix type sustained-release preparation is produced by a simple method, and the dissolution thereof is easily controlled. Hence, the matrix type sustained-release preparation is one of the most commonly used sustained-release preparations. When the matrix type sustained-release preparation is, for example, of a gel matrix type, hydroxypropyl methyl cellulose (hereinafter also called “HPMC”), which is a water-soluble polymer, is used.
Examples of the method for producing a matrix type sustained-release preparation comprising the HPMC include a dry direct tableting method in which a mixture of a drug and the HPMC is directly subjected to tableting, and a wet granulation tableting method in which a mixture of a drug, the HPMC and an additive is granulated together with an appropriate solvent and the resulting granules are dried and then subjected to tableting. Examples of the dry direct tableting method may include, when a drug or the HPMC has insufficient flowability, a dry granulation tableting method in which a mixture after roll compression (dry granulation) is pulverized and then subjected to tableting. Examples of the wet granulation tableting method include the wet granulation tableting method with an agitation granulator and the wet granulation tableting method with a fluidized bed granulator.
The dry direct tableting method is a simple production method and thus is commonly used as the method of producing a matrix type preparation containing HPMC. The dry direct tableting method, however, requires the high content of HPMC in the preparation. Hence, when HPMC having low compressibility is used, the resulting tablet has insufficient strength and may break or crack, or tableting failures such as capping may take place during tableting.
Examples of the additive having high compressibility include crystalline cellulose (JP 06-316535A), low-substituted hydroxypropyl cellulose (JP 2010-254756A), and a hydroxyalkyl alkyl cellulose for tableting (JP 2015-166453A). The hydroxyalkyl alkyl cellulose to be contained by a sustained-release preparation is exemplified by a cellulose derivative having an average particle diameter of 150 to 800 μm (JP 2010-523688T, which is the Japanese phase publication of WO 2008/127794A) and a polysaccharide derivative having a particular particle shape (JP 2014-510137T, which is the Japanese phase publication of WO 2012/138529A).